Hepatitis B virus (HBV) infection remains a major public health problem in the United States (US) with an estimate of up to 2.2 million persons chronically infected. The Hepatitis B Research Network (HBRN) was established in 2008 to address the research priorities identified at the 2008 NIH Consensus Conference on Hepatitis B. The HBRN comprises 13 clinical consortia (21 adult and 7 pediatric clinical centers) in the US and in Toronto, Canada, a data coordinating center, and an immunology center. During the initial funding cycle of HBRN, the investigators developed and implemented an observational cohort study, a clinical trial for patients in the immune tolerant phase and a clinical trial for patients in the immune active phase of HBV infection. This Clinical Center application comprises 2 sites: University of Michigan in Ann Arbor (PI: Dr. Lok) and University of Hawaii/Queen's Medical Center in Honolulu (PI: Dr. Tsai). The Michigan-Hawaii (MI-HI) team has made important contributions to the HBRN studies through enrollment and retention of patients, and data and biospecimen collection. Furthermore, we have played a key role in designing the study protocols and data forms, serving and chairing on HBRN committees, and drafting and editing abstracts and manuscripts. As Chair of the HBRN Steering Committee and Executive Committee since its inception, Dr. Lok has provided leadership in the design and execution of scientific studies, establishing policies for HBRN, and setting up collaboration with industry partners. The specific aims of the MI-HI consortium in the next funding cycle of HBRN are: 1) to continue to enroll patients into HBRN studies and to follow those who have been enrolled to study completion; 2) to contribute to the development of new study proposals making use of data and biospecimens that are collected to further our understanding of the epidemiology, natural history, pathogenesis, and treatment of hepatitis B; and 3) to participate in data analyses and dissemination through abstract presentations and manuscripts. The ancillary study we propose aims to determine: 1) prevalence of co-existent HBsAg and anti- HBs; 2) associating epidemiologic factors; 3) clinical significance; 4) quantitative HBsAg levels and correlation with anti-HBs levels; 5) prevalence of immune escape variants and mixed HBV genotypes/serotypes; and 6) epitope recognition and neutralizing ability of circulating anti-HBs in HBRN participants (adults and children) with co-existent HBsAg and anti-HBs.